It is proposed to investigate the role of citrulline-containing proteins, presumably modified histones, in the neoplastic progression in rabbit skin. These proteins were found associated with chromatin in normal growing rabbit hair follicle cells; in skin papillomas induced by the Shope papilloma virus; and in the Vx2 carcinoma, a malignant derivative of the papilloma. Other tissues did not contain them. Assuming that such modified histones play some role in the expression of the cell genome, it is planned to determine the times at which they appear and disappear in the normal hair growth cycle, to search for mechanisms by which the histones are modified, to determine whether they remain the same or change during the neoplastic progression, to test for their antigenicity and their biological activity in in vitro and in vivo systems, and to determine what effects they have on messenger RNA synthesis.